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Prognostic Implications of Netrin-1 Expression and Its Receptors in Patients with Adenocarcinoma of the Pancreas

  • Hepatic and Pancreatic Cancer
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

To assess the interaction between the expression of netrin-1 or of its receptors to the prognosis of ductal adenocarcinoma of the pancreas.

Methods

In 82 patients with resectable pancreatic adenocarcinoma who underwent curative operation, the expression patterns of netrin-1, deleted in colorectal carcinomas (DCC), UNC5H3, and neogenin were determined by immunohistochemical staining. Kaplan-Meier analysis was performed to assess the prognostic relevance of the examined expression patterns.

Results

Median follow-up was 15 ± 19.9 months (range, 4–108 months). Patients suffering from tumors with no or little expression of netrin-1 (n = 67) had a median recurrence-free survival of 10 months (95% CI, 7–13 months), while a middle to strong expression (n = 15) was associated with a significantly worse median recurrence-free survival of only four months (95% CI, three to five months, p = 0.0165). Overall and recurrence-free survival showed no significant differences between the different expression patterns of DCC, UNC5H3 or neogenin. Netrin-1 expression had significant impact (p = 0.001) on overall survival of patients suffering from poorly differentiated tumors. Stratification according to the nodal status revealed significant influence (p = 0.007) of UNC5H3 expression on the overall survival of patients with pN1 status.

Conclusion

Expression of netrin-1 has significant impact on time to tumor relapse in adenocarcinoma of the pancreas. Netrin-1 expression is associated with worse outcome in poorly differentiated pancreatic adenocarcinomas. Risk-stratification according to the UNC5H3 receptor expression pattern shows that node positive patients (pN1) with no to little UNC5H3 expression carry a significantly worse prognosis than those with middle to strong UNC5H3 expression.

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ACKNOWLEDGMENTS

Financial support for this study was provided by a research grant from the Hamburger Krebsgesellschaft e. V.

We thank Petra Merkert, Antje Heineke, and Petra Schröder for excellent technical assistance. We are grateful to Susanne Pohl for her administrative support in the follow up of patients.

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Authors and Affiliations

  1. Department of General, Visceral and Thoracic Surgery, University Medical Center of Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany

    Björn-Christian Link MD, Matthias Schreiber MS, Jussuf T. Kaifi MD, Robin Wachowiak MD, Dean Bogoevski MD, Guel Cataldegirmen MD, Karim A. Gawad MD, Jakob R. Izbicki MD, FACS & Emre F. Yekebas MD

  2. Department of Pathology, University Medical Center of Hamburg-Eppendorf, Hamburg, Germany

    Uta Reichelt MD, Rana Issa MD & Susann Koops MD

  3. Department of Medical Biometry and Epidemiology, University Medical Center of Hamburg-Eppendorf, Hamburg, Germany

    Michael Bubenheim PhD

Authors
  1. Uta Reichelt MD
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  2. Matthias Schreiber MS
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  3. Jussuf T. Kaifi MD
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  4. Robin Wachowiak MD
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  7. Guel Cataldegirmen MD
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  8. Karim A. Gawad MD
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  11. Jakob R. Izbicki MD, FACS
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Correspondence to Björn-Christian Link MD.

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Link, BC., Reichelt, U., Schreiber, M. et al. Prognostic Implications of Netrin-1 Expression and Its Receptors in Patients with Adenocarcinoma of the Pancreas. Ann Surg Oncol 14, 2591–2599 (2007). https://doi.org/10.1245/s10434-007-9469-6

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  • DOI: https://doi.org/10.1245/s10434-007-9469-6

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